title: Influence of non-alcoholic fatty liver disease on autonomic changes evaluated by the time domain, frequency domain, and symbolic dynamics of heart rate variability.
abstract: BACKGROUND
  Non-alcoholic fatty liver disease (NAFLD) is associated with cardiovascular atherosclerosis independent of classical risk factors. This study investigated the influence of NAFLD on autonomic changes, which is currently unknown.
  
  
  METHODS
  Subjects without an overt history of cardiovascular disease were enrolled during health checkups. The subjects diagnosed for NAFLD using ultrasonography underwent 5-min heart rate variability (HRV) measurements that was analyzed using the following indices: (1) the time domain with the standard deviation of N-N (SDNN) intervals and root mean square of successive differences between adjacent N-N intervals (rMSSD); (2) the frequency domain with low frequency (LF) and high frequency (HF) components; and (3) symbolic dynamics analysis. Routine blood biochemistry data and serum leptin levels were analyzed. Homeostasis model assessment of insulin resistance (HOMA-IR) was measured.
  
  
  RESULTS
  Of the 497 subjects (mean age, 46.2 years), 176 (35.4%) had NAFLD. The HRV indices (Ln SDNN, Ln rMSSD, Ln LF, and Ln HF) were significantly decreased in the NAFLD group (3.51 vs 3.62 ms, 3.06 vs 3.22 ms, 5.26 vs 5.49 ms(2), 4.49 vs 5.21 ms(2), respectively, all P<0.05). Ln SDNN was significantly lower in the NAFLD group after adjustment for age, sex, hypertension, dyslipidemia, metabolic syndrome, body mass index, smoking, estimated glomerular filtration rate, HOMA-IR, and leptin (P<0.05). In the symbolic dynamic analysis, 0 V percentage was significantly higher in the NAFLD group (33.8% vs 28.7%, P = 0.001) and significantly correlated with linear HRV indices (Ln SDNN, Ln rMSSD, and Ln HF).
  
  
  CONCLUSIONS
  NAFLD is associated with decreased Ln SDNN and increased 0 V percentage. The former association was independent of conventional cardiovascular risk factors and serum biomarkers (insulin resistance and leptin). Further risk stratification of autonomic dysfunction with falls or cardiovascular diseases by these HRV parameters is required in patients with NAFLD.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Liu
authors.forename: Chi-Sheng
authors.initials: CS
authors.lastname: Hung
authors.forename: Yen-Wen
authors.initials: YW
authors.lastname: Wu
authors.forename: Yi-Chin
authors.initials: YC
authors.lastname: Lee
authors.forename: Yen-Hung
authors.initials: YH
authors.lastname: Lin
authors.forename: Chen
authors.initials: C
authors.lastname: Lin
authors.forename: Men-Tzung
authors.initials: MT
authors.lastname: Lo
authors.forename: Chun-Chieh
authors.initials: CC
authors.lastname: Chan
authors.forename: Hsi-Pin
authors.initials: HP
authors.lastname: Ma
authors.forename: Yi-Lwun
authors.initials: YL
authors.lastname: Ho
authors.forename: Chien-Hung
authors.initials: CH
authors.lastname: Chen
mesh_terms: D000328:Adult; D000367:Age Factors; D050197:Atherosclerosis / Q000097:blood / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D015992:Body Mass Index; D003920:Diabetes Mellitus / Q000097:blood / Q000000981:diagnostic imaging / Q000503:physiopathology*; D005234:Fatty Liver / Q000097:blood / Q000150:complications / Q000000981:diagnostic imaging / Q000503:physiopathology*; D005260:Female; D005919:Glomerular Filtration Rate; D006339:Heart Rate; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000150:complications / Q000000981:diagnostic imaging / Q000503:physiopathology*; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000150:complications / Q000000981:diagnostic imaging / Q000503:physiopathology*; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D012307:Risk Factors; D012737:Sex Factors; D014463:Ultrasonography
chemical_list: D020738:Leptin