Cardiac Autonomic Markers Partly Account for Adiposity-Related Liver Enzyme Variation in Non-Diabetic Adults With...

To quantify the extent to which cardiac autonomic markers account for the associations between adiposity and liver enzyme levels in non-diabetic adults with overweight or obesity.

The clinical discovery cohort included 432 non-diabetic adults with overweight or obesity. Body mass index (BMI) and waist-to-height ratio (WHtR) were exposures; alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transferase (GGT) were outcomes. Resting mean heart rate and heart rate variability (HRV) were assessed as cardiac autonomic markers. Multivariable regression and mediation analyses were performed. Supportive analyses included 21 383 UK Biobank participants.

Higher BMI and WHtR were associated with higher liver enzyme levels, higher resting mean heart rate and lower HRV in the clinical cohort. Resting mean heart rate was the most consistent cardiac autonomic mediator, accounting for 16.6%-27.5% of the associations between BMI and liver enzyme levels and 17.8%-36.9% of those for WHtR. HRV indices accounted for 10.1%-28.2% and 8.8%-29.9% of the corresponding associations, respectively. After inclusion of the homeostatic model assessment of insulin resistance (HOMA-IR) as a parallel mediator, indirect effects through cardiac autonomic markers remained statistically significant, particularly for ALT. In UK Biobank, resting pulse rate accounted for 5.83%-9.47% of the associations between adiposity and liver enzyme levels.

Higher resting heart rate and lower HRV partly accounted for cross-sectional associations between adiposity and liver enzyme levels. Cardiac autonomic markers warrant further evaluation as complementary physiological measures in studies of obesity-related liver enzyme variation.