DataSheet_1_Autonomic Imbalance Increases the Risk for Non-alcoholic Fatty Liver Disease.docx

BackgroundAlthough autonomic imbalance is associated with an increased risk for metabolic disease, its effects on nonalcoholic fatty liver disease (NAFLD) remains unclear. We aimed to evaluate whether autonomic dysfunction predicts the risk for nonalcoholic fatty liver disease (NAFLD).
MethodsA total of 33,899 participants without NAFLD who underwent health screening programs between 2011 and 2018 were enrolled. NAFLD was identified by ultrasonography. Autonomic activity was estimated using heart rate variability (HRV). Time domain [standard deviation of the normal-to-normal interval (SDNN) and root mean square difference (RMSSD)]; frequency domain [total power (TP), low frequency (LF), and high frequency (HF), and LF/HF ratio were analyzed.
FindingsA total 6,466 participants developed NAFLD within a median of 5.7 years. Subjects with incident NAFLD showed decreased overall autonomic modulation and vagal activity with lowered SDNN, RMSSD, HF, normalized HF, compared to those without NAFLD. As the SDNN, RMSSD, TP, LF, and HF tertiles increased, the risk of NAFLD decreased with tertile 1 being the reference group [the hazard ratios (95% confidence intervals) of tertile 3 were 0.90 (0.85–0.96), 0.83 (0.78–0.88), 0.91 (0.86-0.97), 0.93 (0.87-0.99) and 0.89 (0.83-0.94), respectively] after adjusting for potential confounders. The risk for NAFLD was significantly higher in subjects in whom sustained elevated heart rate, normalized LF, and LF/HF ratio values than in those with sustained decrease in these parameters during follow-up.
ConclusionsOverall autonomic imbalance, decreased parasympathetic activity, and recently increased sympathetic activity might increase the risk of NAFLD.

研究背景
尽管自主神经失衡与代谢疾病的发病风险升高相关，但其对非酒精性脂肪性肝病（NAFLD）的影响仍尚不明确。本研究旨在评估自主神经功能障碍是否可预测非酒精性脂肪性肝病（NAFLD）的发病风险。

研究方法
本研究纳入2011至2018年间接受健康筛查、且基线无非酒精性脂肪性肝病（NAFLD）的33899名参与者。采用超声检查确诊NAFLD。通过心率变异性（heart rate variability, HRV）评估自主神经活动，分析时域指标[正常窦性RR间期标准差（standard deviation of the normal-to-normal interval, SDNN）及相邻RR间期差值的均方根（root mean square difference, RMSSD）]与频域指标[总功率（total power, TP）、低频功率（low frequency, LF）、高频功率（high frequency, HF）以及LF/HF比值]。

研究结果
中位随访5.7年内，共计6466名参与者新发NAFLD。与基线无NAFLD的参与者相比，新发NAFLD者的整体自主神经调节功能及迷走神经活动均降低，表现为SDNN、RMSSD、HF及标准化HF水平下降。以第一三分位组为参照，随着SDNN、RMSSD、TP、LF及HF三分位水平升高，NAFLD的发病风险逐渐降低；校正潜在混杂因素后，第三三分位组的风险比（95%置信区间）分别为0.90（0.85~0.96）、0.83（0.78~0.88）、0.91（0.86~0.97）、0.93（0.87~0.99）及0.89（0.83~0.94）。随访期间持续存在心率升高、标准化LF及LF/HF比值升高的参与者，其NAFLD发病风险显著高于上述参数持续降低的参与者。

研究结论
整体自主神经失衡、副交感神经活动降低以及近期交感神经活动增强，可能会升高NAFLD的发病风险。