Abstract
Reduced heart rate variability (HRV) is reflective of autonomic imbalance. However, its impact on non-alcoholic fatty liver disease (NAFLD) is unknown. We investigated the association between 10-s HRV and incident NAFLD. A cohort of 154,286 Korean adults with no NAFLD at baseline were followed up. 10-s electrocardiograms were used to estimate two time-domain HRV, the standard deviation of normal-to-normal intervals (SDNN) and the root mean square of successive differences in RR intervals (RMSSD). Hepatic steatosis (HS) and liver fibrosis were assessed using ultrasonography and the fibrosis-4 index (FIB-4). A total of 27,279 incident HS (median follow up of 4.2 years) and 1250 incident HS plus high FIB-4 (median follow up of 4.2 years) cases were identified at follow-up. The multivariable adjusted hazard ratios (aHRs) (95% confidence intervals [CIs]) in a model with time-dependent variables for incident HS, comparing the lowest quintile to the highest and reference quintile of the RMSSD, was 1.43 (1.37–1.49), and the corresponding HR for incident HS plus intermediate/high FIB-4 was 1.70 (1.35–2.15). Similarly, SDNN was inversely associated with incident HS and HS plus intermediate/high FIB-4. The results were similar using the NAFLD fibrosis score. Autonomic imbalance assessed by HRV may help to identify individuals at a high risk of HS and its progression and warrant further studies.
Highlights
Reduced heart rate variability (HRV) is reflective of autonomic imbalance
The associations between potential confounders with HRV and Hepatic steatosis (HS) are presented in Supplementary Tables 6–8. In this large-scale cohort study of apparently healthy adults, low HRV, measured by the standard deviation of normal-to-normal intervals (SDNN) and root mean square of successive differences (RMSSD), which reflect global autonomic regulation and parasympathetic activity of the heart, respectively, were associated with increased risk of both incident HS and HS plus intermediate/high fibrosis markers based on fibrosis-4 index (FIB-4) or NAFLD fibrosis score (NFS). This association was observed when changes in HRV and confounders during follow-up were treated as time-varying covariates and was independent of a wide range of potential confounders, including sleep duration and depressive symptoms, which influence H RV18,19
Our findings indicate that autonomic nervous system (ANS) function estimated by HRV may play an independent role in non-alcoholic fatty liver disease (NAFLD) risk and severity
Summary
Reduced heart rate variability (HRV) is reflective of autonomic imbalance. its impact on non-alcoholic fatty liver disease (NAFLD) is unknown. 10-s electrocardiograms were used to estimate two time-domain HRV, the standard deviation of normal-to-normal intervals (SDNN) and the root mean square of successive differences in RR intervals (RMSSD). Abbreviations ALT Alanine aminotransferase ANS Autonomic nervous system AST Aspartate aminotransferase BMI Body mass index BP Blood pressure CES-D Centre for Epidemiologic Studies Depression CI Confidence interval hs-CRP High-sensitivity C-reactive protein CVD Cardiovascular disease ECG Electrocardiography GGT Gamma-glutamyl transferase HDL-C High-density lipoprotein cholesterol FIB-4 Fibrosis-4 scores HEPA Health-enhancing physical activity. HOMA-IR Homeostatic model assessment–insulin resistance HR Hazard ratio HRV Heart rate variability HS Hepatic steatosis HSI Hepatic Steatosis Index LDL-C Low-density lipoprotein cholesterol NAFLD Non-alcoholic fatty liver disease NFS NAFLD fibrosis score PNS Parasympathetic nervous system PSQI Pittsburgh Sleep Quality Index RMSSD Root mean square of successive differences in RR intervals SDNN Standard deviation of normal-to-normal intervals SNS Sympathetic nervous system. As there are currently no licensed drugs available for the treatment of NAFLD, it is of considerable importance to identify modifiable risk factors and manage them to prevent this d isease[10–12]
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