Search

Although there is a link between obstructive sleep apnea (OSA) and atrial fibrillation (AF) and numerous investigations have examined the mechanism of AF development in OSA patients, which includes cardiac remodeling, inflammation, and gap junction-related conduction disorder, there is limited information regarding the differences between the sexes. This study analyzes the impact of sex differences on the expression of cardiac remodeling, inflammatory cytokines, and gap junctions in patients with OSA and AF. A total of 154 individuals diagnosed with sleep-related breathing disorders (SRBDs) were enrolled in the study and underwent polysomnography and echocardiography. Significant OSA was defined as an apnea–hypopnea index (AHI) of ≥15 per hour. Exosomes were purified from the plasma of all SRBD patients and incubated in HL-1 cells to investigate their effects on inflammatory cytokines and GJA1 expression. The differences in cardiac remodeling and expression of these biomarkers in both sexes were analyzed. Of the 154 enrolled patients, 110 patients were male and 44 patients were female. The LA sizes and E/e’ ratios of male OSA patients with concomitant AF were greater than those of control participants and those without AF (all p < 0.05). Meanwhile, female OSA patients with AF had a lower left ventricular ejection fraction than those OSA patients without AF and control subjects (p < 0.05). Regarding the expression of inflammatory cytokines and GJA1, the mRNA expression levels of GJA1 were lower and those of IL-1β were higher in those male OSA patients with AF than in those male OSA patients without AF and control subjects (p < 0.05). By contrast, mRNA expression levels of HIF-1α were higher in those female OSA patients with and without AF than in control subjects (p < 0.05). In conclusion, our study revealed sex-specific differences in the risk factors and biomarkers associated with AF development in patients with OSA.

Obstructive sleep apnea syndrome (OSAS) is an important risk factor for atrial fibrillation (AF). GJA1 gene encoding connexin43, a major protein in cardiac gap junctions, plays a crucial role in the synchronized contraction of the heart and in cardiac arrhythmia. However, little is known regarding the role of GJA1 expression in the incidence of AF in patients with OSAS. All prospectively enrolled OSAS patients underwent polysomnography, electrocardiography, a 24-h Holter test, and echocardiography. Moderate-to-severe OSAS was defined as an apnea-hypopnea index (AHI) ≥ 15. Exosomes were purified from the plasma of all OSAS patients and incubated in HL-1 cells to investigate the effect of exosomes from patients with and without AF on GJA1 expression. A total of 129 patients were recruited for this study; 26 were excluded due to an AHI < 15. Of the 103 enrolled patients, 21 had AF, and 82 did not. Multivariate analysis showed diabetes mellitus, lower sleep efficiency, lower left ventricular ejection fraction, and larger left atrial (LA) size were independent predictors of AF occurrence in OSAS patients. The area under the receiver operating characteristic curve for LA with a size ≥38.5 mm for predicting AF occurrence in OSAS patients was 0.795 (95% confidence interval [0.666, 0.925]); p < 0.001). GJA1 expression in HL-1 cells incubated with exosomes from OSAS patients with AF was lower than that with exosomes from patients without AF after controlling for age and sex and was negatively correlated with the AHI and oxygen desaturation index (ODI), especially during the non-rapid eye movement period (NREM) of OSAS patients with AF (all p < 0.05). LA size was an independent predictor of AF occurrence in OSAS patients. The AHI and ODI in the NREM period of OSAS patients with AF were negatively correlated with GJA1 expression in HL-1 cells, which offers a hint that GJA1 may play a crucial role in the development of AF in patients with OSAS.