The Impact of Non-alcoholic Fatty Liver Disease on Autonomic Control of Heart Rate Variability

• Main Authors: Yu-Chun Liu, 劉宇浚
• Other Authors: 何奕倫
• Format: Others
• Language: zh-TW
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/12388945857648881477

碩士 === 國立臺灣大學 === 臨床醫學研究所 === 100 === Non-alcoholic fatty liver disease (NAFLD) refers to a spectrum of liver disorders, ranging from simple steatosis to steatohepatitis (NASH), advanced fibrosis, and cirrhosis. In Taiwan, the prevalence of NAFLD was 11.5% to 41% in adult population. The cardiovascular disease (CVD) is the second leading cause of death in NAFLD patients. The pathogenesis of NAFLD is attributed to a multi-hit process mainly involving insulin resistance and oxidative stress. The NAFLD was associated with obesity, type 2 diabetes mellitus (DM), dyslipidemia and metabolic syndrome (MS) in many experimental and clinical studies. The NAFLD is now considered to be the hepatic manifestation of metabolic syndrome, although the nature of their relationship remains debated. Several reports showed the associations of NAFLD with carotid and coronary atherosclerosis independently of classical risk factors of CVD. Abnormal cardiac autonomic function was associated with CVD in the Framinghan heart study and the ARIC study. Heart rate variability (HRV) is an established tool for assessment of cardiac autonomic function. Decreased HRV represents the autonomic dysfunction. The associations between decreased HRV and hypertension, DM, dyslipidemia and MS have been demonstrated. The impact of NAFLD on HRV has not been reported. Besides, the leptin has been shown to cause sympathetic activation and its serum level is elevated in NAFLD patients. Therefore, we hypothesize that the sympathetic activation due to insulin resistance and increased leptin might cause decreased HRV in NAFLD patients. We designed a cross-sectional study and recruited 1000 subjects from Aug 2010 to Feb 2012 at the health checkup center of the Far Eastern Poly Clinic. The subjects with documented CVD, congestive heart failure and endstage renal disease were excluded. We defined one group of subjects with NAFDL and another without NAFLD as the control group. Fatty liver was confirmed if at least one of the following three findings were present: increased liver echogenicity with evident contrast between liver and kidney; the blurring of vessels; and deep attenuation of the ultrasound signal. To exclude other causes of NAFLD, the subjects with a weekly intake of alcohol over 140g in male and 70g in female, hepatitis B, hepatitis C infection and use of drugs that may induce NAFLD were excluded from the group of NAFLD. The subjects underwent 5-minutes HRV measurements by an ambulatory Holter electrocardiogram in supine position. The HRV was analyzed by the following indices: 1) the time domain with the standard deviation of NN (SDNN) intervals, rMSSD (root mean square of successive differences between adjacent N-N intervals); and 2) the frequency domain with the low frequency (LF) and high frequency (HF) power. Data were expressed as the natural logarithm (ln) of the above HRV indices. The result of blood test, family history and medical history such as previous systemic and liver disease, medication, alcohol intake and smoking status were collected. In the total 1000 subjects, 497 subjects received the blood test of fasting insulin and letpin. The clinical characteristics were compared by the Student’s t test for continuous variables and Chi-Square test for categorical variables. In the 497 subjects with fasting insulin and leptin data, the HRV indices (Ln SDNN, Ln rMSSD, Ln HF and Ln HF) was significantly decreased in the NAFLD group ( 3.50 vs 3.64 ms, 3.04 vs 3.23 ms, 5.27 vs 5.49 ms2, 4.84 vs 5.24 ms2; all p <0.05). In the 497 subjects, NAFLD was negatively associated with Ln SDNN, after adjustment for the effects of age, sex, hypertension, dyslipidemia, MS, body mass index, smoking, estimated glomerular infiltration rate, homeostasis model assessment of insulin resistance and leptin (p <0.05). In conclusion, NAFLD is associated with decreased HRV independent of classic cardiovascular risk factors, insulin resistance and letpin.