LDL-C modifies the association between triglycerides and depression identified by threshold scanning in US adults

Previous studies of the relationship between lipid levels and depression have yielded inconsistent findings. This inconsistency may relate to inter-lipid interactions. The current study employs a novel analytical approach to evaluate interactions among lipid parameters in relation to the odds of depression. This study utilized datasets obtained from the U.S. National Health and Nutrition Examination Survey spanning 2005 to 2018. Depressive symptoms were assessed using the Patient Health Questionnaire-9, with a score ≥ 10 used to define depression. Survey-weighted generalized linear models first tested interaction effects between continuous triglyceride (TG) and cholesterol subtypes (low-density lipoprotein cholesterol LDL-C, high-density lipoprotein cholesterol, total cholesterol). For statistically significant interactions, participants were dichotomized at each of 39 quantile points (2.5-97.5% at 2.5% intervals) of lipid 2. Sequential analyses determined whether these binary subgroups significantly modified the association between lipid 1 and depression. The optimal lipid 2 cutoff value was selected based on the multiple-comparison-adjusted P value for interaction across all quantiles. Sensitivity analyses evaluated cutoff value stability. A total of 8962 participants were included. The interaction analysis revealed a synergistic effect between TG and LDL-C on depression (interaction term β = 0.158, P = 0.03). Sequential interaction threshold analysis identified LDL-C = 3.6 mmol/L as the most significant effect modifier. In the subgroup with LDL-C levels ≥ 3.6 mmol/L, TG were significantly positively associated with depression (odds ratio 1.78; 95% confidence interval 1.30-2.42; P interaction = 0.002). Sensitivity analyses incorporating eight distinct analytical conditions consistently confirmed LDL-C = 3.6 mmol/L as a significant effect modifier of the TG-depression association. TG showed a significant positive association with depression in the context of high LDL-C, with 3.6 mmol/L emerging as an optimal threshold for identifying this interaction effect. This finding underscores the importance of considering lipid-lipid interactions when evaluating the link between lipid profiles and depression.