Sleep quality partially mediates the association between remnant cholesterol inflammatory index and depressive symptoms: multi-cohort analysis from cross-sectional and longitudinal cohorts.

OBJECTIVE: Previous studies have reported a cross-sectional association between the remnant cholesterol inflammatory index (RCII) and depressive symptoms. However, longitudinal evidence remains limited. This study aimed to examine the associations between RCII, depressive symptoms, and sleep quality, and to assess the mediating role of sleep quality and potential sex differences. METHODS: Using data from three nationally representative cohorts-NHANES (n = 7,359, USA, cross-sectional), CHARLS (n = 4,551, China, longitudinal), and ELSA (n = 4,808, UK, longitudinal). Multivariable regression models were used to evaluate associations of RCII with depressive symptoms and sleep quality. Mediation analyses were conducted to estimate the indirect effect of sleep quality, with stratification by sex. RESULTS: Higher RCII levels were consistently associated with greater odds of depressive symptoms after multivariable adjustment in NHANES (OR = 1.16, 95% CI: 1.09-1.24), CHARLS (OR = 1.11, 95% CI: 1.04-1.18), and ELSA (OR = 1.12, 95% CI: 1.03-1.21). Elevated RCII was also significantly associated with poorer sleep quality in NHANES (β = 0.05, P < 0.001), CHARLS (β = 0.02, P = 0.049), and ELSA (β = 0.03, P < 0.001). Poorer sleep quality was, in turn, associated with higher odds of depressive symptoms across all cohorts. Mediation analyses demonstrated significant indirect effects of sleep quality on the association between RCII and depressive symptoms, with adjusted ACMEs of 0.0044 (95% CI: 0.0024-0.0067; P < 0.001), 0.0003 (95% CI: 0.0001-0.0008; P = 0.044), and 0.0005 (95% CI: 0.0004-0.0010; P < 0.001) in NHANES, CHARLS, and ELSA, respectively. Significant direct effects also remained after adjustment, with ADEs of 0.0080 (95% CI: 0.0032-0.0132; P = 0.002), 0.0114 (95% CI: 0.0051-0.0176; P < 0.001), and 0.0076 (95% CI: 0.0004-0.0137; P = 0.036), respectively. The corresponding proportions mediated were 35.41% (95% CI: 20.03%-59.79%), 3.30% (95% CI: 0.17%-10.68%), and 6.17% (95% CI: 5.13%-17.08%), respectively. CONCLUSIONS: This multinational study provides evidence linking metabolic inflammation, as reflected by RCII, with both depressive symptoms and poor sleep quality. The identification of sleep quality as a partial mediator suggests that sleep disturbance may represent a potential pathway underlying the association between metabolic dysregulation and depression. These findings suggest that RCII may help identify individuals at elevated risk of depressive symptoms, underscoring the importance of integrated strategies targeting metabolic health and sleep in the prevention and management of depressive symptoms.