Atrial fibrillation (AF) is the most common arrhythmia in the clinical setting and an independent risk factor for stroke. Approximately 10 million Chinese people are affected by AF, but the genetic basis is largely unknown. A recent genome-wide association study in Iceland identified association between SNP rs2200733 on 4q25 and AF; however, many independent replication studies are essential to unequivocally validate this association. To assess the association between rs2200733 and AF as well as that between rs2200733 and ischemic stroke in a mainland Chinese Han population, we carried out case-control association studies with 383 AF patients versus 851 non-AF controls and 811 ischemic stroke patients versus 688 non-stroke controls. Highly significant association was detected between rs2200733 and AF in a Chinese Han population (allelic P = 3.7 × 10(-11) with OR = 1.81; genotypic P = 4.1 × 10(-12) with a dominant model). When the AF cases were divided into lone AF (32.6%) and other types of AF (67.4%), significantly stronger association was found with lone AF (OR = 2.40, P = 1.3 × 10(-9) compared to OR = 1.59, P = 6.2 × 10(-7) for other types of AF; P = 0.02 for two ORs). No significant association was found between rs2200733 and ischemic stroke. Our results suggest that SNP rs2200733 confers a highly significant risk of AF, but not ischemic stroke, in a more representative Chinese Han population in the mainland China.

Atrial fibrillation (AF) is the most common cardiac rhythm disorder at the clinical setting and accounts for up to 15% of all strokes. Recent genome-wide association studies (GWAS) identified two single nucleotide polymorphisms (SNPs), rs2106261 and rs7193343 in ZFHX3 (zinc finger homeobox 3 gene) and rs13376333 in KCNN3 (encoding a potassium intermediate/small conductance calcium-activated channel, subfamily N, member 3) that showed significant association with AF in multiple populations of European ancestry. Here, we studied a Chinese Han, GeneID cohort consisting of 650 AF patients and 1,447 non-AF controls to test whether the GWAS findings on ZFHX3/KCNN3 and AF can be expanded to a different ethnic population. No significant association was detected for rs7193343 in ZFHX3 and rs13376333 in KCNN3. However, significant association was identified between rs2106261 in ZFHX3 and AF in the GeneID population for both allelic frequencies (P = 0.001 after adjusting for covariates of age, gender, hypertension, coronary artery disease, and diabetes mellitus; OR = 1.32), and genotypic frequencies assuming either an additive or recessive model (OR = 1.29, P = 0.001 and OR = 1.77, P = 0.00018, respectively). When only lone AF cases were analyzed, the association remained significant (OR = 1.50, P = 0.001 for allelic association; OR = 1.45, P = 0.001 for an additive model; OR = 2.24, P = 0.000043 for a recessive model). Our results indicate that rs2106261 in ZFHX3 confers a significant risk of AF in a Chinese Han population. The study expands the association between ZFHX3 and AF to a non-European ancestry population and provides the first evidence of a cross-race susceptibility of the 16q22 AF locus.

BackgroundThe association between dyslipidemia, a major risk factor for cardiovascular diseases, and atrial fibrillation (AF) is not clear because of limited evidence.Hypothesis.Dyslipidemia may be associated with increased risk of AF in a Chinese population.MethodsA total of 88 785 participants free from AF at baseline (2006–2007) were identified from the Kailuan Study. Fasting levels of total cholesterol (TC), low‐density lipoprotein cholesterol (LDL‐C), high‐density lipoprotein cholesterol (HDL‐C), and triglycerides (TG) were measured at baseline using standard procedures. The study population was stratified based on quartiles of lipid profile. Incident AF was ascertained from electrocardiograms at biennial follow‐up visits (2008–2015). The associations between incident AF and the different lipid parameters (TC, LDL‐C, HDL‐C, and TG) were assessed by Cox proportional hazards regression analysis.ResultsOver a mean follow‐up period of 7.12 years, 328 subjects developed AF. Higher TC (hazard ratio [HR]: 0.60, 95% confidence interval [CI]: 0.43‐0.84) and LDL‐C (HR: 0.60, 95% CI: 0.43‐0.83) levels were inversely associated with incident AF after multivariable adjustment. HDL‐C and TG levels showed no association with newly developed AF. The results remained consistent after exclusion of individuals with myocardial infarction or cerebral infarction, or those on lipid‐lowering therapy. Both TC/HDL‐C and LDL‐C/HDL‐C ratios were inversely associated with risk of AF (per unit increment, HR: 0.88, 95% CI: 0.79‐0.98 and HR: 0.77, 95% CI: 0.66‐0.91, respectively).ConclusionsTC and LDL‐C levels were inversely associated with incident AF, whereas no significant association of AF with HDL‐C or TG levels was observed.

Background Insomnia is the most prevalent sleep disorder; however, little research has explored the link between insomnia and atrial fibrillation (AF). Hypothesis Insomnia is associated with increased risk of AF in a Chinese population. Methods A total of 8371 Chinese participants (4314 males; mean age, 42.4 ± 13.1 years) were enrolled in this cross‐sectional study to investigate the association between insomnia and AF. AF was assessed in a standard supine resting position with a 10‐s 12‐lead electrocardiograph (ECG) or by self‐reported history. Insomnia was assessed using the Athens Insomnia Scale (AIS), and a score of ≥6 was regarded as having insomnia. The association between insomnia and AF was determined by logistic regression analysis. Results Among the 8371 subjects, 1074 (12.8%) had different degrees of insomnia, and AF was observed in 50 subjects (0.60%). After adjusting for potential confounders, individuals with insomnia had moderately increased likelihood of suffering from AF compared with those without insomnia (odds ratio [OR]: 1.92, 95% confidence interval [CI]: 1.00‐3.70, P = 0.05). After stratifying data by age, a significant positive association was found in those age <40 years (OR: 6.52, 95% CI: 1.64‐25.83, P = 0.01), and a similar trend existed in males after stratifying by sex, although this relationship was not statistically significant (OR: 2.11, 95% CI: 0.92‐4.83, P = 0.08). Conclusions Individuals with insomnia may have a higher risk of AF in the particular Chinese population assessed in this study. Age (<40 years) is a significant factor in the association between insomnia and AF.

Backgrounds. Segmental and circumferential pulmonary vein isolations (SPVI and CPVI) have been demonstrated to be effective therapies for paroxysmal atrial fibrillation (PAF). PVI is well established as the endpoint of different ablation techniques, whereas it may not completely account for the long-term success. Methods. 181 drug-refractory symptomatic PAF patients were referred for segmental or circumferential PVI (SPVI = 67; CPVI = 114). Heart rate variability (HRV) was assessed before and after the final ablation. Results. After following up for 62.23 ± 12.75 months, patients underwent 1.41 ± 0.68 procedures in average, and the success rates in SPVI and CPVI groups were comparable. 119 patients were free from AF recurrence (SPVI-S, n = 43; CPVI-S, n = 76). 56 patients had recurrent episodes (SPVI-R, n = 21; CPVI-R, n = 35). Either ablation technique decreased HRV significantly. Postablation SDNN and rMSSD were significantly lower in SPVI-S and CPVI-S subgroups than in SPVI-R and CPVI-R subgroups (SPVI-S versus SPVI-R: SDNN 91.8 ± 32.6 versus 111.5 ± 36.2 ms, rMSSD 47.4 ± 32.3 versus 55.2 ± 35.2 ms; CPVI-S versus CPVI-R: SDNN 83.0 ± 35.6 versus 101.0 ± 40.7 ms, rMSSD 41.1 ± 22.9 versus 59.2 ± 44.8 ms; all P < 0.05). Attenuation of SDNN and rMSSD remained for 12 months in SPVI-S and CPVI-S subgroups, whereas it recovered earlier in SPVI-R and CPVI-R subgroups. Multivariate logistic regression analysis identified SDNN as the only predictor of long-term success. Conclusions. Beyond PVI, denervation may be a common mechanism underlying different ablation strategies for PAF.

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BackgroundGrowing evidence indicates that advanced glycation end-product receptor (RAGE) might play a contributory role in the pathogenesis of coronary artery disease (CAD). To shed some light from a genetic perspective, we sought to investigate the interactive association of RAGE gene four common polymorphisms (rs1800625 or T-429C, rs1800624 or T-374A, rs2070600 or Gly82Ser, and rs184003 or G1704A) with the risk of developing CAD in a large northeastern Han Chinese population.Methodology/Principal FindingsThis was a hospital-based case-control study incorporating 1142 patients diagnosed with CAD and 1106 age- and gender-matched controls. All individuals were angiographically confirmed. Risk estimates were expressed as odds ratio (OR) and 95% confidence interval (CI). Overall there were significant differences in the genotype and allele distributions of rs1800625 and rs184003, even after the Bonferroni correction. Logistic regression analyses indicated that rs1800625 and rs184003 were associated with significant risk of CAD under both additive (OR = 1.20 and 1.23; 95% CI: 1.06–1.37 and 1.06–1.42; P = 0.006 and 0.008) and recessive (OR = 1.75 and 2.39; 95% CI: 1.28–2.40 and 1.47–3.87; P<0.001 and <0.001) models after adjusting for confounders. In haplotype analyses, haplotypes C-T-G-G and T-A-G-T (alleles in order of rs1800625, rs1800624, rs2070600 and rs184003), overrepresented in patients, were associated with 52% (95% CI: 1.19–1.87; P = 0.0052) and 63% (95% CI: 1.14–2.34; P = 0.0075) significant increases in adjusted risk for CAD. Further interactive analyses identified an overall best multifactor dimensionality reduction (MDR) model including rs1800625 and rs184003. This model had a maximal testing accuracy of 0.6856 and a cross-validation consistency of 10 out of 10 (P = 0.0016). The validity of this model was substantiated by classical Logistic regression analysis.ConclusionsOur findings provided strong evidence for the potentially contributory roles of RAGE multiple genetic polymorphisms, especially in the context of locus-to-locus interaction, in the pathogenesis of CAD among northeastern Han Chinese.

Background: Atrial electrical remodeling (AER) is the underlying mechanism of atrial fibrillation (AF). The present study investigated the impact of epicardial fat pad (FP) ablation on acute AER (AAER) and inducibility of AF. Methods and Results: AAER was performed in 28 mongrel dogs through 4-h rapid atrial pacing (RAP). Before RAP, 14 dogs (ablation group) underwent FP ablation, and the other 14 (control group) underwent a sham procedure. The atrial effective refractory period (ERP) and vulnerability window (VW) of AF were measured with and without bilateral cervical vagosympathetic nerve stimulation (VNS) at the high right atrium, ostium of the coronary sinus (CS) and distal CS before and after every hour of RAP. In the control group, ERP was markedly shortened in the first 2 h of RAP and then stabilized. AF was only slightly induced. After RAP, the time course of ERP with and without VNS was similar. VNS significantly shortened ERP and increased VW before and after RAP. In the ablation group, ERP was significantly prolonged after FP ablation. Moreover, neither VNS nor RAP shortened the ERP or increased the VW. AF could not be induced (VW=0).Conclusions: RAP resulted in AAER, which may be mediated and aggravated by autonomic activity. Epicardial FP ablation generated denervation, which not only abolishes AF inducibility but also prevents RAP-mediated AAER. (Circ J 2010; 74: 885 - 894)