Vascular aging mediates the association between atherogenic lipid profiles and depression: survey-weighted evidence from NHANES 2005-2020.

BACKGROUND

Dyslipidemia and depressive symptoms often co-occur, but the pathway linking atherogenic lipids to mood is unclear. Vascular aging, indexed by aortic stiffness, may mediate this relationship.

METHODS

We analyzed nine cycles of the National Health and Nutrition Examination Survey (2005-2020). Adults ≥20 years with complete data on lipids, estimated pulse-wave velocity (ePWV), and the Patient Health Questionnaire-9 (PHQ-9) were included (n = 17,599). Exposures were the atherogenic index of plasma (AIP), triglyceride-to-HDL-cholesterol ratio (TG/HDL-C), and HDL cholesterol. The mediator was ePWV, and the outcome was moderate-to-severe depressive symptoms (PHQ-9 ≥ 10). Survey-weighted regression and mediation models with 5000 bootstraps adjusted for sociodemographic, lifestyle, and clinical covariates.

RESULTS

Overall, 8.7 % had moderate-to-severe depressive symptoms. Higher AIP and TG/HDL-C were associated with greater odds of depression (per SD AIP: adjusted odds ratio [OR], 1.59; 95 % CI, 1.30-1.97; per unit TG/HDL-C: OR, 1.04; 95 % CI, 1.03-1.05), while HDL cholesterol showed inverse association (per mg/dL: adjusted odds ratio [OR], 0.98; 95 % CI, 0.97-0.99). AIP was positively related to ePWV (β, 0.43 m/s; 95 % CI, 0.30-0.56). ePWV was independently associated with depression (OR per 1 m/s, 1.11; 95 % CI, 1.06-1.16). Mediation indicated that ePWV explained 10.4 % of the AIP-depression association, 8.2 % for TG/HDL-C, and 6.4 % for HDL cholesterol in overall study population. Mediation occurred in both sexes, with larger proportions mediated in women.

CONCLUSIONS

Atherogenic lipid phenotypes were linked to depressive symptoms, with vascular aging explaining part of this association, especially in women. These findings support vascular aging as a pathway connecting dyslipidemia to mood and motivate longitudinal studies targeting lipid quality and large-artery stiffness.