Blood urea nitrogen-to-lipid ratios are novel indices inversely associated with anxiety: Insights from NHANES

Anxiety is a highly prevalent mental disorder linked to metabolic and renal dysregulation. Blood urea nitrogen (BUN) and lipid profiles have been associated with affective symptoms, but findings are inconsistent, indicating the limitations of the single indicator. Therefore, this study proposed novel BUN-to-lipid indicators and investigated their associations with anxiety.

We analyzed 5167 adults extracted from NHANES 2007-2012. Four novel BUN-to-lipid ratios, BLR (BUN/LDL-C), BHR (BUN/HDL-C), BRR (BUN/remnant cholesterol), and BTR (BUN/total cholesterol) were calculated. Statistical analyses included multivariable logistic regression, restricted cubic spline analysis, subgroup analysis, and machine learning development.

All four BUN-to-lipid ratios showed significant inverse associations with anxiety. BTR demonstrated the strongest inverse effect (OR = 0.51, 95 %CI:0.41-0.62, p < 0.001, unadjusted Model 1). Restricted cubic spline analysis revealed significant nonlinear associations with L-shaped patterns for all four indices (P for overall <0.001; P for nonlinear <0.001). Subgroup analyses demonstrated consistent inverse effects of BUN-to-lipid indicators across most demographics and clinical factors, although stronger associations in middle and elderly aged adults were observed. Furthermore, machine learning development ranked BTR and BLR as top predictors, outperforming individual lipids and BUN alone.

Composite BUN-to-lipid ratios are independently and non-linearly associated with lower odds of anxiety. These composite BUN-to-lipid biomarkers represent novel indicators of renal-metabolic dysregulation in anxiety pathophysiology, offering strategies for early risk assessment and clinical monitoring.