Abstract
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.
Highlights
Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases in modernized countries and has a rapidly increasing global prevalence [1,2,3]
Overall autonomic imbalance, decreased parasympathetic activity, and recently increased sympathetic activity might increase the risk of nonalcoholic fatty liver disease (NAFLD)
The heart rate variability (HRV) indices standard deviation of the normal-to-normal interval (SDNN), RMSSD, high frequency (HF), and HF norm were lower, whereas heart rate, low frequency (LF), LF norm, and LF/HF ratio were higher in the NAFLD group than in the control group (Table 2)
Summary
Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases in modernized countries and has a rapidly increasing global prevalence [1,2,3]. Dyslipidemia, and insulin resistance have been regarded as well-known risk factors for fatty liver [4]. Imbalance in the autonomic nervous system (ANS) as an early signal of insulin resistance and metabolic diseases has been reported to have clinical implications [6]. Previous studies have shown a relationship between hepatic steatosis and autonomic dysfunction [7,8,9,10]. These were small-sized, single-center, and crosssectional studies. 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)
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