Beyond inflammation and cholesterol: atherogenic index of plasma mediates the link between hsCRP/HDL-C ratio and depression in US adults NHANES 2015–2020

BACKGROUND: Dyslipidemia and inflammation play key roles in the pathophysiology of depression and are significantly associated with the plasma atherogenic index (AIP). However, a reliable biomarker for diagnosing depression remains elusive. The hsCRP/HDL-C ratio, combining C-reactive protein (hs-CRP) and high-density lipoprotein cholesterol (HDL-C), may serve as a potential composite indicator. OBJECTIVE: This study aims to explore the relationship between the hsCRP/HDL-C ratio and depression. METHODS: NHANES data (2015-2020) from 10,357 participants were analyzed. Depression was assessed using the PHQ-9, and dyslipidemia with AIP. Participants were grouped based on their hsCRP/HDL-C ratio. Statistical methods included Student's t-test, chi-square test, logistic regression, restricted cubic spline (RCS) model, and mediation analysis. RESULTS: RCS regression analysis showed a nonlinear relationship between the hsCRP/HDL-C ratio and depression. The two-piece logistic regression model was used to calculate the threshold effect, and the likelihood ratio test (p < 0.05) indicated that the inflection point for hs-C/H was 11.608. When the hsCRP/HDL-C ratio was below this threshold, a positive correlation with depression was observed (OR: 1.04, 95% CI: 1.01-1.07). When the hsCRP/HDL-C ratio was equal to or greater than the threshold, a negative correlation was found (OR: 0.99, 95% CI: 0.97-1.00). Subgroup analysis showed consistent results, with marital status being the only factor that significantly influenced this relationship. Mediation analysis revealed that AIP partially mediated the relationship between hsCRP/HDL-C ratio and depression, explaining 11.2% of the total effect (95% CI: 2.26%-27.00%). CONCLUSIONS: A higher hsCRP/HDL-C ratio is associated with increased depression risk. Interventions targeting CRP levels and lipid abnormalities may help reduce this risk.