The Mediating Role of Inflammation in the Association Between NHHR and Pelvic Inflammatory Disease: A Case-Control Study Based on Machine Learning.

Background: Pelvic inflammatory disease (PID) is a common infection among women of reproductive age, primarily caused by sexually transmitted pathogens such as Chlamydia trachomatis and Neisseria gonorrhoeae. Emerging evidence suggests that lipid metabolism may contribute to systemic inflammation and increased susceptibility to PID. This study aimed to explore the association between the non-high-density lipoprotein to high-density lipoprotein cholesterol ratio (NHHR) and PID, and to assess the mediating role of inflammatory markers. Methods: This retrospective case-control study included 2,247 women diagnosed with or without PID based on surgical and clinical records at a single tertiary hospital. Least absolute shrinkage and selection operator (LASSO) regression was used to identify candidate predictors, followed by multivariate logistic regression. A PID prediction model was developed and evaluated using training and validation datasets (7:3 split). Mediation analysis assessed the role of inflammatory markers, particularly white blood cell (WBC) count. Results: NHHR was significantly associated with PID (OR = 1.39, 95% CI = 1.16-1.66). Mediation analysis showed that WBC partially mediated the NHHR-PID relationship, accounting for 19.26% of the effect. The prediction model demonstrated strong discrimination, with AUCs of 0.825 (training) and 0.819 (validation). Conclusion: Higher NHHR levels are associated with an increased risk of PID, and systemic inflammation may partially mediate this relationship. NHHR may serve as a potential marker for PID risk stratification, though further external validation is warranted.