U-shaped association between myeloperoxidase levels and anxiety risk: a cross-sectional study in a Chinese population

This study investigates the association between myeloperoxidase (MPO) levels and anxiety risk in Chinese adults and explores potential effect modifiers, with implications for neuroinflammatory biomarker-guided anxiety prevention strategies.

Using cross-sectional data from 30,418 adults undergoing routine health examinations (July 2020-June 2021), anxiety severity was assessed via the Self-Rating Anxiety Scale (SAS; score ≥ 50 as clinically relevant). Plasma MPO was quantified by ELISA. Multivariate logistic regression, restricted cubic splines (RCS), threshold effect analysis, and subgroup interactions were conducted to evaluate nonlinear associations.

A U-shaped relationship between MPO and anxiety risk was identified. In fully adjusted models, participants in the lowest (Q1: ≤29.77 ng/mL, OR = 1.15, 95% CI: 1.03-1.28, p = 0.01) and highest quintiles (Q5: ≥47.3 ng/mL, OR = 1.17, 95% CI: 1.05-1.31, p = 0.004) exhibited significantly elevated anxiety risks compared to the reference quintile (Q2: 29.8-34.7 ng/mL). RCS analysis confirmed a nonlinear association (p for nonlinearity < 0.01), with an inflection point at 30 ng/mL: below this threshold, each 1 ng/mL MPO increase reduced anxiety risk (OR = 0.982, CI: 0.970-0.994), while levels above it heightened risk (OR = 1.004, CI: 1.001-1.008). Diabetes mellitus significantly modified this relationship (p-interaction = 0.028), with diabetic individuals showing amplified risks at higher plasma MPO (Q5 OR = 1.84 vs. non-diabetic Q5 OR = 1.15).

Plasma MPO demonstrates a U-shaped association with anxiety risk independent of cardiometabolic confounders. Diabetic individuals exhibit heightened susceptibility to MPO-related anxiety, suggesting synergistic neuroinflammatory pathways. Monitoring MPO may aid in risk stratification and personalized interventions, particularly in populations with diabetes.