BACKGROUND:Cardiovascular diseases (CVDs) account for a large and increasing health burden worldwide, as shown in the Global Burden of Disease Study 2021. However, there has been no comprehensive assessment of CVDs in Asia, which bears the largest population globally. OBJECTIVES:This study sought to evaluate the burden of CVD in Asia from 1990 to 2021. METHODS:Mortality, prevalence, and disability-adjusted life years (DALYs) along with their age-standardized rates (ASRs) per 100,000 population from 1990 to 2021 were used to measure the CVDs burden. Further subanalyses were conducted based on age group and sex. RESULTS:In 2021, CVDs caused an estimated 11.9 million deaths (95% uncertainty interval [UI]: 10.9-12.9 million deaths), 340.4 million prevalent cases (95% UI: 315.1-366.9 million prevalent cases), and 270.4 million DALYs (95% UI: 251.6-290.2 million DALYs). Although the ASR of prevalence slightly increased from 1990 to 2021 with a percentage change of 5.7% (95% UI: 3.9%-8.1%), the ASRs of death and DALYs were significantly decreased, with percentage changes of -28.2% (95% UI: -42.2% to -12.5%) and -37.8% (95% UI: -50.5% to -24.3%), respectively. The Asian burden of CVDs was higher in males and the elderly. The primary contributors to DALYs across Asia were ischemic heart disease, stroke, and hypertensive heart disease. CONCLUSIONS:Burden of CVDs in Asia remains substantial. Certain populations, including males and the elderly, experienced a heavier burden of CVDs.

BACKGROUND AND AIMS:Quantifying the multidimensional risk that subclinical liver disease imposes on cardiovascular health remains a critical unmet need. This study aimed to investigate the independent and synergistic associations of hepatic steatosis, fibrosis, and functional decline with incident cardiovascular disease (CVD). METHODS:In this prospective cohort study of 318 308 participants free of clinical liver and CVD at baseline, this study evaluated the association of three non-invasive liver biomarkers-fatty liver index (FLI) for steatosis, fibrosis-4 index (FIB-4) for fibrosis, and albumin-bilirubin (ALBI) score for functional reserve-with major incident CVD events, including myocardial infarction, heart failure, atrial fibrillation, ischaemic stroke, and cardiovascular death. RESULTS:Over a median follow-up of 14.0 years, 32 637 incident CVD events (10.3%) occurred. Each biomarker independently predicted CVD risk after multivariable adjustment: the highest quartile (Q4) of FLI (adjusted hazard ratio [aHR] 1.46, 95% confidence interval [CI] 1.40-1.52), FIB-4 (aHR 1.66, 95% CI 1.60-1.73), and ALBI (aHR 1.42, 95% CI 1.37-1.47) showed significantly elevated risks compared to Q1. Critically, participants with all three biomarkers in Q4 exhibited a substantially elevated synergistic risk (aHR 2.53, 95% CI 2.38-2.70). Sex-specific analyses revealed FLI was more strongly associated with CVD in women, whereas FIB-4 and ALBI showed greater risk in men. Results were consistent across sensitivity analyses and specific CVD endpoints. CONCLUSIONS:These findings establish subclinical liver disease-through steatosis, fibrosis, and functional impairment-as an independent and synergistic determinant of CVD risk. Incorporation of these non-invasive biomarkers could refine CVD risk stratification and enable targeted prevention strategies.

Cardioneuroablation (CNA) is a novel procedure that shows promising results in patients with functional bradyarrhythmia, including functional sinus node dysfunction (SND) and atrioventricular block (AVB). We performed a systematic review and meta-analysis to evaluate the efficacy and safety of CNA in this population. PubMed, Embase and Web of Science were searched from January 2005 to August 2025 following PRISMA guidelines. A single-arm proportion meta-analysis was performed using a random effects model. Nineteen observational studies comprising 482 patients with functional bradyarrhythmia who underwent CNA were included (mean age 38.1 ± 5.1 years; 55.7% male). Over a mean follow-up of 16.3 ± 3.6 months, the pooled recurrence rate was 13.1% (95% confidence interval [CI] 9.5% - 17.8%; I2 = 0%) and the pooled complication rate was 1.0% (95% CI 0.1% - 9.1%; I2 = 0%). Subgroup analyses suggested lower recurrence rates with functional SND (9.7% [6.3%-14.6%]; I2 = 0%), biatrial ablation (11.0% [6.7%-17.5%]; I2 = 10.7%), and the use of extracardiac noncontact vagal stimulation (ECVS) (8.3% [2.7%-22.9%]; I2 = 0%). No significant differences were observed among techniques used to identify ganglionated plexi (p = 0.938). Data synthesis indicated a non-significant trend towards increased heart rate, as well as shorter sinus node recovery time (SNRT) and corrected SNRT after CNA. These findings support that CNA may be effective and safe in functional SND and AVB; however, the overall certainty of evidence is low, and larger, well-designed clinical trials are required to inform future guideline recommendations.

BACKGROUND:Vagal response (VR) was thought to the successful rate in catheter ablation of atrial fibrillation (AF). However, little is known about VR during pulmonary vein isolation (PVI) in AF and heart failure (HF). This study aims at investigating the incidence, risk factors and clinical outcomes of VR during PVI in paroxysmal AF with HF. METHODS:A total of 551 paroxysmal AF patients were enrolled and classified according to HF status: without HF, HF with preserved, reduced and mildly reduced ejection fraction. The VR was defined as atrioventricular block, asystole or an increase in the R-R interval by 50% during ablation. RESULTS:VR had the same occurrence rate between patients without HF and those with HFpEF (63 [20.5%] vs. 22 [18.9%], p = 0.722). However, VR were less frequently observed in HFmrEF and HFrEF(3 [5.0%] and 2 [2.9%], p = 0.004 and < 0.001 compared with without HF, respectively). Left ventricular EF ≥ 50% was independently associated with intraprocedural VR by multivariable analysis (p = 0.007). Patients with HFrEF or HFmrEF showed a higher mean and slower heart rate with decreased heart rate variability than those without HF. After 18.3 ± 7.4 months' follow-up, 2 of 22 (9.0%) HFpEF patients with VR and 12 of 94 (12.8%) without VR had AF recurrence (p = 0.942). Four HFrEF or HFmrEF patients with VR maintained sinus rhythm during 18.3 ± 4.9 months' follow-up. CONCLUSION:Intraprocedural VR is not uncommon in HFpEF but is rarely observed in HFmrEF and HFrEF. Autonomic nervous system remodeling in HF, manifesting as a decrease in heart rate variability, might be the underlying reason. VR does not indicate a better clinical outcome in HFpEF.

Background Atrial fibrillation (AF) is the most common sustained arrhythmia worldwide and imposes a substantial clinical burden. Epicardial adipose tissue (EAT), the cardiac visceral fat depot, has been implicated in AF pathogenesis, but the cellular, molecular, and immune features underlying EAT‐mediated AF remain elusive. Methods We combined population‐based analysis, Mendelian randomization, single‐nucleus RNA sequencing, and biomarker validation. The visceral adipose tissue–AF association was examined in the National Health and Nutrition Examination Survey, genetic evidence was evaluated using Mendelian randomization based on UKB (UK Biobank), EAT was profiled in patients with coronary artery disease (6 with AF, 3 without), and key circulating signals were evaluated in the Fuwai Hospital cohort and UKB. Results Higher visceral adipose tissue was associated with increased AF risk in National Health and Nutrition Examination Survey, and Mendelian randomization provided genetic evidence consistent with a potential causal contribution of visceral adipose tissue to AF. Single‐nucleus RNA sequencing showed extensive EAT remodeling in patients with coronary artery disease and AF, including impaired neuroprotective and myelin‐maintenance programs, metabolic imbalance, profibrotic activation, and a chronic inflammatory milieu with immunoglobulin G–related humoral immune activation. Drug2cell prioritized candidate drug–cell associations across specific EAT cell populations, and summary data–based Mendelian randomization prioritized PTPRN2 as a putative AF susceptibility gene. Higher plasma interleukin‐17 levels were associated with postoperative AF in the Fuwai Hospital cohort, whereas circulating interleukin‐17C and interleukin‐17D were independently associated with incident AF in the UKB. Conclusions We constructed the first single‐nucleus transcriptomic atlas of human AF‐related EAT and identified potential mechanisms linking EAT remodeling to arrhythmogenesis. Elevated plasma interleukin‐17 may serve as a predictive biomarker for AF.

BACKGROUND:Autonomic function may play a crucial role in the pathogenesis of vasovagal syncope (VVS). However, the characteristics of autonomic function across different VVS subtypes remain unclear. Deceleration capacity (DC), a novel vagal indicator, may offer improved discriminatory value. OBJECTIVE:To evaluate the ability of DC to distinguish between different subtypes of VVS. METHODS:Patients with VVS confirmed by a positive head-up tilt test were included. All heart rate variability (HRV) and DC data were obtained from 24-h Holter monitoring and analyzed among different subtypes using ANOVA, logistic regression, and ROC analyses. A DC-based subtype prediction model was further developed. RESULTS:Among 141 patients (40 ± 18 years; 54 males), 36 (25.5%) had cardioinhibitory VVS, 20 (14.2%) vasodepressor, and 85 (60.3%) mixed type. Significant differences across subtypes were observed in minimum HR, maximum HR, SDNN, VLF, LF/HF and DC (all p < 0.05). Among these parameters, DC showed the strongest discriminatory ability in differentiating patients with cardioinhibitory responses (cardioinhibitory and mixed types) from those without (vasodepressor type), outperforming traditional HRV indices (p < 0.05). A predictive model based on daytime DC achieved an AUC of 0.811 (95% CI: 0.731-0.89). Each 1-ms increase in daytime DC was associated with a 33.3% higher odds of a cardioinhibitory response. CONCLUSION:Baseline autonomic function varies among VVS subtypes and vagal indicators like DC might help predict patient subtypes.

BACKGROUND:Although tissue contact significantly affects pulsed field ablation (PFA) efficacy, evidence supporting contact force-guided PFA for recurrent left atrial flutter (AFL) remains scarce. In this study we investigated the efficacy and safety of PFA in this difficult-to-treat population compared with radiofrequency ablation (RFA). METHODS:Patients with atypical AFL who had undergone at least 1 previous persistent atrial fibrillation ablation were prospectively enrolled for PFA and compared with a retrospectively analyzed control group treated with conventional RFA at the same period. Coronary artery spasm risk was assessed via coronary angiography. The efficacy end points were recurrence of atrial arrhythmias after a 3-month blanking period. The safety end point included severe procedure-related complications. RESULTS:A total of 253 patients were included in this study (mean age 59 years, 68% male), 119 patients received PFA treatment, 134 patients received RFA. At 12-month follow-up, the RFA group demonstrated a significant higher atrial tachyarrhythmia recurrence rate compared with the PFA group (36% vs 24%; log rank P = 0.027). In the multivariable Cox regression model, PFA was linked to lower risk of the recurrence risk compared with RFA (hazard ratio, 0.56; 95% confidential interval, 0.35-0.90; P = 0.017). Moreover, acute mitral isthmus block rate in the PFA group was significantly higher than in the RFA group (100% vs 64%; P < 0.001). No procedure-related complications were observed, including esophageal fistula, phrenic nerve injury, and coronary artery spasm. CONCLUSIONS:In patients with refractory left AFL post atrial fibrillation ablation, contact force-guided PFA appears promising and demonstrates favourable efficacy compared with conventional RFA.

BACKGROUND:The autonomic effects of pulsed-field ablation (PFA) remain incompletely defined. Previous work has relied on heart rate variability (HRV), which cannot differentiate sympathetic from vagal activity. We used deceleration capacity (DC) and acceleration capacity (AC)-valid vagal/sympathetic activity measures-to evaluate autonomic changes before and after PFA for paroxysmal atrial fibrillation (PAF). OBJECTIVE:The study aimed to characterize peri-PFA changes in DC/AC in patients with PAF. METHODS:This prospective study included 45 consecutive patients with PAF who experienced PFA. DC/AC and HRV were performed at baseline, immediately after ablation, and at 3-month follow-up. The relationship between HRV and DC/AC was assessed using Pearson correlation. Receiver operating characteristic analyses were used to evaluate the predictive value of DC/AC for atrial fibrillation (AF) recurrence. Kaplan-Meier analysis assessed freedom from AF recurrence over 12 months in relation to autonomic indices. RESULTS:Pulmonary vein isolation was successful in all patients; 91.1% exhibited intraprocedural vagal responses. DC and |AC| decreased immediately after PFA and partially recovered at 3 months (overall P < .05 for both). Most HRV parameters had weak correlations with DC/AC (Pearson r = 0.08-0.67). At 12 months, the drug-free atrial tachycardia-free rate was 75.56%. Preablation DC/AC (area under the curve 0.63/0.64) and changes in DC/AC (area under the curve 0.68/0.67) were able to predict AF recurrence. Patients with lower preablation |AC| and smaller ΔDC/ΔAC had significantly higher AF recurrence rates (log-rank P < .05). CONCLUSION:Our evaluation via DC/AC revealed significant alterations in autonomic activity after PFA. Furthermore, DC/AC and their trajectories demonstrated moderate predictive value for AF recurrence, underscoring the need to reconsider the impact of PFA on cardiac autonomic innervation.

Background:Pulsed field ablation (PFA) is effective for atrial fibrillation, but its real-world performance for cavotricuspid isthmus (CTI)-dependent atrial flutter remains inadequately defined. Objective:The purpose of this study was to systematically evaluate the efficacy and safety of PFA for CTI ablation using real-world evidence. Methods:A total of 9 observational studies (656 patients) published up to January 2026 were analyzed using a random-effects model. Results:Pooled analysis revealed a short-term bidirectional CTI block rate of 99.4% and a short-to-midterm recurrence rate of 2.14%. Mean CTI ablation time was highly efficient (8.86 minutes). Incidences of catastrophic complications and permanent atrioventricular block were 0%. The overall incidence of intraprocedural right coronary artery spasm was 2.0%. Prophylactic high-dose intravenous nitroglycerin (>1 mg) significantly reduced coronary spasm incidence compared with low-dose (≤1 mg) regimens (1% vs 8%; P = .0016). Sensitivity analyses confirmed spasm risk was independent of PFA catheter configuration (P = .9549). Conclusion:PFA is a rapid, safe, and highly effective modality for CTI ablation. The risk of transient coronary spasm may be mitigated with prophylactic high-dose nitroglycerin. These hypothesis-generating findings warrant further validation.

BACKGROUND:Atrial fibrillation (AF) independently increases dementia risk, but whether accelerometer-measured physical activity (PA) modifies this association remains unquantified, particularly against self-reported PA limitations. METHODS:Prospective analysis of 91,795 UK Biobank participants with valid accelerometer data (median age 57, 42.9 % male; 2800 with baseline AF). We categorized whether measured activity met the standard recommendation [moderate-to-vigorous physical activity (MVPA) >_150 min/week]. Questionnaire-derived MVPA data from 353,643 UK Biobank participants (median age 57, male: 46.7 %) between 2006 and 2010 were used for validation. The primary outcome was the diagnosis of incident all-cause dementia. We also assessed correlation between accelerometer-derived and self-reported activity. RESULTS:Over 7.6-year median follow-up, AF was significantly associated with a higher dementia risk [Adjusted hazard ratio (aHR): 1.76, 95 % confidential interval (CI): 1.51-2.05]. Guideline-adherent PA was associated with a lower AF-related dementia risk to non-significance (aHR: 1.36, 95 %CI: 0.96-1.91). Moreover, PA may be associated with higher protection effect on dementia risk in AF patients (aHR: 0.55, 95 % CI: 0.33-0.92) than in non-AF (aHR: 0.81, 95 % CI: 0.69-0.96), although without statistical difference (Pinteraction = 0.213). Correlation between accelerometer-derived and selfreported MVPA was weak (Spearman r = 0.155, 95 % CI: 0.148-0.162). Self-reported activity was not associated with a decreased risk of dementia in both AF and non-AF participants. CONCLUSION:Higher accelerometer-measured PA is associated with lower AF-associated dementia risk. Future prospective studies with extended follow-up and serial activity monitoring are needed to confirm these findings.

Background Vasovagal syncope (VVS) might be associated with alterations in vagal activity. Cardiac acceleration capacity (AC) is a novel index related to autonomic modulation. It remains unknown whether AC could be used to assess vagal tone and differentiate VVS patients. Objectives This study aimed to investigate the association between AC and VVS, and evaluate the capability of AC to identify VVS susceptibility. Methods In this observational study, 204 VVS patients (41.2 ± 16.9 years, 40.2% [82 of 204] men) were included, of whom 87.3% (178 of 204) VVS patients had positive responses to tilt-table testing, and 116 asymptomatic individuals were included as controls. Twenty-four-hour Holter monitoring was performed for all participants. Multivariate logistic regression analysis and receiver-operating characteristic curves were performed for heart rate variability metrics. Results VVS patients exhibited significantly higher AC than control subjects (8.81 ± 2.21 ms vs 5.89 ± 1.27 ms; P < 0.001). AC correlated with deceleration capacity (VVS: r = 0.90 [95% CI: 0.83-0.96]; controls: r = 0.92 [95% CI: 0.85-1.00]) and other vagal-dominant heart rate variability metrics. In multivariate models, increased AC was significantly associated with an elevated risk of VVS (adjusted OR: 3.54 [95% CI: 2.55-4.91]). Daytime AC showed strong discriminative power for VVS (area under curve 0.910 [95% CI: 0.879-0.942]), and outperformed nighttime measures in the identification of VVS. Conclusions Higher AC was observed in VVS patients during the nonsyncopal period, indicative of AC’s potential association with vagal modulation. Daytime AC showed superior performance in detecting VVS susceptibility, offering a noninvasive approach to assisting clinical diagnosis.

Whether hepatic steatosis, as indexed by the fatty liver index (FLI), is associated with incident atrial fibrillation (AF) among adults with diabetes beyond shared cardiometabolic risk factors remains uncertain. To investigate the association between fatty liver index and incident atrial fibrillation in adults with diabetes. We analyzed 29,341 UK Biobank participants with baseline diabetes and no history of atrial fibrillation or atrial flutter, and no prior cardiovascular disease. FLI was evaluated both categorically (< 30, 30–59, 60–89, ≥ 90) and continuously using restricted cubic splines. Incident AF was identified through linked health records, with death treated as a competing risk. Cox models were sequentially adjusted for demographics, lifestyle, socioeconomic status, and metabolic factors; Fine–Gray models were also applied. Sensitivity analyses included 1:10 propensity score matching (FLI ≥ 60 vs. < 60). Among participants with FLI ≥ 30, AF risk was further stratified by the number of metabolic abnormalities (hypertension, obesity, dyslipidemia), grouped as 0, 1, 2, or ≥ 3. Over a median follow-up of 14.1 years (13.4–14.7), 2,890 incident AF events occurred. AF incidence rose across FLI categories, from 4.88 (95

BACKGROUND:The bidirectional liver-heart axis is increasingly recognized. Although compelling evidence links liver fibrosis to adverse cardiovascular outcomes, its specific link to sudden cardiac arrest (SCA) in the general population remains less well elucidated. OBJECTIVE:We aimed to investigate the association between liver fibrosis and SCA. METHODS:This prospective analysis included 452,454 participants from the United Kingdom Biobank. Liver fibrosis was non-invasively assessed using the Fibrosis-4 (FIB-4) index, with participants categorized into low (<1.30), indeterminate (1.30-2.67), and high (>2.67) risk groups. The primary outcome was incident SCA. Associations were evaluated using Cox proportional hazards models, adjusted for comprehensive cardiovascular risk factors. RESULTS:The analysis included participants with a median age of 58 years, and 45.8% were male. During a median follow-up of 13.8 years, 2889 incident SCA cases were documented. Participants with higher FIB-4 scores exhibited significantly higher cumulative incidence of SCA (log-rank P < .001). Compared with the low-risk group, the adjusted hazard ratios for SCA were 1.26 (95% confidential interval [CI]: 1.15-1.39) in the indeterminate-risk group and 1.69 (95% CI: 1.36-2.12) in the high-risk group. Dose-response analysis revealed a nonlinear yet positive association between continuous FIB-4 index and SCA risk. Each standard deviation increase in FIB-4 was associated with a 20% higher SCA risk (adjusted hazard ratios 1.20, 95% CI: 1.15-1.27). CONCLUSION:Liver fibrosis, as assessed by the FIB-4 index, is an independent and graded predictor of SCA risk in the general population. This readily available biomarker could enhance SCA risk stratification and primary prevention strategies.

Introduction: Atrial fibrillation (AF) is a prevalent cardiac arrhythmia. Pulmonary vein isolation (PVI) is a cornerstone for catheter ablation for AF. Most recently, pulsed-field ablation (PFA) has emerged as a novel technique that minimizes tissue damage due to its tissue selectivity with promising clinical success. Despite its promise, the impact of PFA on cardiac autonomic function following PVI, particularly heart rate variability (HRV), and the differences between catheter ablation (CA) techniques, remain unclear. Methods: Following PRISMA guidelines, we conducted a systematic review and meta-analysis to evaluate changes in HRV parameters in three months post-catheter ablation using PFA, cryoballoon (CRYO), and radiofrequency (RF) ablation techniques. We searched databases including PubMed, Embase, Scopus, and Web of Science for relevant studies, focusing on HRV metrics such as SDNN, LF and HF in AF patients undergoing CA. Results: Our meta-analysis included 35 studies involving 6,267 AF patients. The results demonstrated a significant increase in heart rate and a decrease in HRV parameters such as SDNN and LF following CA in three months. Subgroup analyses revealed variations across ablation techniques, with PFA showing a milder impact on autonomic function compared to CRYO and RF. Notably, PFA was associated with a lower AF recurrence rate, suggesting superior therapeutic efficacy. Conclusion: PFA demonstrates a lower effect on cardiac autonomic function than the other two ablation techniques in three months. Notably, PFA showed a trend toward superior treatment outcomes, which may inform future choices of ablation technique for PVI in AF management. Further research is warranted to explore long-term autonomic effects and optimize treatment protocols.

Acute myocardial infarction is a leading cause of morbidity and mortality, with ischaemia–reperfusion (I/R) injury exacerbating myocardial damage. Vagus nerve stimulation (VNS) has been reported to exert cardioprotective effects, but its efficacy in preconditioning against I/R injury requires further investigation. We evaluated the cardioprotective effects of VNS preconditioning in a rat model of acute myocardial infarction with induced I/R injury. Sixty rats were randomized into Pre‐VNS, Control and Sham groups. The Pre‐VNS group received 1 week of low‐level cervical VNS before induction of I/R injury; stimulation was deactivated 30 min before ischaemia. Survival, echocardiographic function, reperfusion arrhythmias, arrhythmia inducibility, infarct size, apoptosis and inflammatory cytokines were assessed. Survival did not differ significantly between Pre‐VNS and Control groups (75.0% vs. 65.0%, p = 0.497). However, Pre‐VNS animals exhibited preserved cardiac function, with higher ejection fraction and fractional shortening ( p < 0.001). VNS preconditioning reduced the incidence of reperfusion arrhythmia during left anterior descending coronary artery ligature release ( p = 0.006) and decreased the arrhythmia index on programmed stimulation ( p = 0.003). Infarct size and cardiomyocyte apoptosis were significantly attenuated ( p < 0.001), accompanied by markedly lower serum interleukin‐1β, interleukin‐6 and tumour necrosis factor‐alpha levels ( p < 0.001). VNS preconditioning effectively mitigates I/R injury by improving cardiac function, reducing infarct size and arrhythmias, and attenuating inflammatory and apoptotic responses.

Hemodialysis patients are at high risk for ICU admission due to elevated mortality, cardiovascular disease, and infection rates. Traditional ICU scoring systems (e.g., APACHE-II, SOFA) demonstrate limited accuracy in this population. This study aimed to identify key risk factors and develop interpretable machine learning (ML) models for predicting ICU outcomes to enable early intervention. This multicenter study analyzed data from three cohorts: The First Affiliated Hospital of Sun Yat-sen University (n = 248), MIMIC-IV (n = 769), and eICU-CRD (n = 1,878). Primary outcome was all-cause ICU mortality; secondary outcomes were cardiovascular and infection-related mortality. Thirteen ML algorithms and ensemble models were applied to 113 clinical variables collected within 24 h of ICU admission. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and benchmarked against existing ICU scoring systems. We employed SHapley Additive exPlanation (SHAP) analysis to enhance interpretability. Key predictors numbered 6 (cardiovascular mortality), 11 (infection-related mortality), and 25 (all-cause mortality). Ensemble machine learning models, trained on the SYSU cohort, were initially screened by performance (8-fold cross-validation AUC ≥ 0.80) and evaluated in the eICU selection cohort, with the top-performing models subsequently validated in the external MIMIC-IV cohort. In the external validation, NeuralNetC achieved the highest AUC of 0.847 (95

Background: The interplay between dietary patterns, epigenetic aging, and cardiovascular-kidney-metabolic (CKM) syndrome remains poorly understood. This study investigated the associations of the Dietary Inflammatory Index (DII) and Dietary Oxidative Balance Score (DOBS) with CKM stages, epigenetic age acceleration (DNAmAA), and mortality, as well as the mediating role of DNAmAA in these relationships. Methods: Data from the National Health and Nutrition Examination Survey (NHANES) 1999–2002 were analyzed, including 2,109 non-pregnant adults aged ≥20 years. DII and DOBS were derived from 24-hour dietary recalls. CKM stages (0–4) were defined based on metabolic disorders, chronic kidney disease, and cardiovascular disease. DNAmAA was calculated using multiple epigenetic clocks. Multivariable-adjusted regression models assessed associations, and mediation analysis evaluated the role of DNAmAA in mortality outcomes. Results: Higher DII (pro-inflammatory diet) was significantly associated with advanced CKM stages (OR for Tertile 3 vs. Tertile 1: 1.97, 95% CI: 1.38–2.80, P=0.001) and accelerated GrimAge (OR: 3.63, 95% CI: 2.32–5.70, P<0.001) and DunedinPoAm (OR: 1.19, 95% CI: 1.08–1.28, P<0.001). Conversely, higher DOBS (antioxidant-rich diet) correlated with lower CKM risk (OR for Tertile 3: 0.62, 95% CI: 0.44–0.89, P=0.017) and slower epigenetic aging. Anti-inflammatory/antioxidant diets showed the strongest protective effects. Mediation analysis revealed that GrimAge2Mort and DunedinPoAm significantly mediated the associations of DII (proportion mediated: 23.2% and 10.7%, respectively, P<0.001) and DOBS (16.3% and 7.5%, P<0.001) with all-cause mortality, with similar trends for cardiovascular death. Conclusions: Pro-inflammatory diets are linked to worse CKM outcomes and accelerated epigenetic aging, while antioxidant-rich diets exhibit protective effects. Epigenetic aging, particularly GrimAge and DunedinPoAm, partially mediates the diet-mortality relationship. These findings highlight the potential of dietary interventions to mitigate CKM progression and reduce mortality risk through epigenetic mechanisms.

BACKGROUND:Atrial fibrillation (AF) significantly increases stroke, heart failure, and mortality risk. Elevated lipoprotein(a) (Lp[a]) is implicated in AF pathogenesis, but its relationship with systemic inflammation (assessed by high-sensitivity C-reactive protein [hs-CRP]) remains unclear. OBJECTIVE:We investigated whether the Lp(a)-AF association is independent of baseline inflammatory status. METHODS:In this retrospective cohort study, we analyzed 365,899 United Kingdom (UK) Biobank participants without baseline AF. Lp(a) was modeled as a continuous exposure (per 50 nmol/L increase) and categorically (≥125 nmol/L). Systemic inflammation was defined as hs-CRP ≥2 mg/L. Multivariable Cox proportional hazards models (adjusted for age, sex, cardiovascular risk factors, and comorbidities) and Fine-Gray competing risk analyses estimated adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident AF. RESULTS:Over a median 13.5-year follow-up, 25,048 (6.8%) incident AF cases occurred. Elevated Lp(a) (7.44% vs 6.77%, log-rank P < .001) and hs-CRP (8.49% vs 5.96%, log-rank P < .001) were associated with higher incident AF. Cox proportional hazard model adjusted for covariates, higher Lp(a) (≥125 nmol/L) was associated with increased AF risk regardless of hs-CRP levels for AF (hs-CRP ≥2 mg/L: HR, 1.12; 95% CI, 1.06-1.19; P < .001; hs-CRP <2 mg/L: HR, 1.09; 95% CI, 1.04-1.15; P = .001). Results remained consistent in propensity score matched cohorts and sensitivity analyses. CONCLUSION:Lp(a) is an independent risk factor for AF, irrespective of baseline inflammatory status, as measured by hs-CRP.

BACKGROUND AND AIMS:It remains unknown whether the brain glymphatic system, which is driven by the heartbeat-driven pulsation of arteries and is responsible for cerebral waste clearance, is impaired in atrial fibrillation (AF) and mediates cognitive dysfunction related to AF. The aim of this study was to assess brain glymphatic alterations in AF, their role in cognitive function, and whether catheter ablation can improve glymphatic activity. METHODS:In this case-control and prospective before-and-after study, patients with AF and healthy controls (HCs) were enrolled. Participants underwent brain magnetic resonance imaging and a comprehensive neuropsychological battery. Glymphatic activity was quantified by diffusion tensor image analysis along the perivascular space (DTI-ALPS) index. Magnetic resonance imaging was repeated after surgery in patients who underwent ablation. RESULTS:Overall, 87 patients with AF and 44 HCs were enrolled. Compared with HCs, patients with AF had a lower ALPS index (P = .016). Nonparoxysmal AF patients showed lower ALPS index than both HCs (P = .002) and paroxysmal AF patients (P = .044). A lower ALPS index was associated with worse scores of Trail Making Test, Digit Symbol Substitution Test, Digit Span Test, and Stroop Colour and Word Test (all P < .05). Mediation analyses revealed that glymphatic activity was a mediator between AF and cognitive decline. Among the 50 patients who underwent ablation therapy, DTI-ALPS index was improved after surgery (P = .015). CONCLUSIONS:Brain glymphatic function measured by DTI-ALPS index was impaired in patients with AF, mediates the association between AF and cognitive decline, and was improved after ablation therapy.