Indirect pathways linking hypertension and depression: a multiple mediation analysis using national population data

Background

Hypertension and depression are highly prevalent conditions that frequently co-occur and contribute substantially to global disease burden. Although previous studies have reported an association between hypertension and depressive symptoms, the underlying mechanisms remain insufficiently understood. In particular, it is unclear whether this relationship reflects a direct biological effect or operates indirectly through behavioral, metabolic, and subjective health-related pathways. The present study aimed to investigate the interrelationship between hypertension and depression using a multiple mediation framework, with a focus on identifying modifiable mediating factors and clarifying the relative contribution of each pathway.

Methods

We analyzed pooled cross-sectional data from the Korea National Health and Nutrition Examination Survey (KNHANES) spanning 2016 to 2024. Adults aged 18 years and older were included in the analysis. Depression was defined as a Patient Health Questionnaire-9 (PHQ-9) score ≥10. Hypertension status was derived from standardized clinical variables. Potential mediators included behavioral factors (high-risk alcohol consumption, current smoking, aerobic physical activity), subjective health status, weight change, and metabolic conditions (obesity, diabetes mellitus, and hypercholesterolemia). Complex survey design elements, including stratification, clustering, and sampling weights, were incorporated. Multiple mediation analysis was conducted using structural equation modeling with robust maximum likelihood estimation to simultaneously evaluate direct and indirect effects.

Results

In the fully specified model, the direct effect of hypertension on depression was not statistically significant (c′ = −0.002, p = 0.724), suggesting the absence of a direct association after accounting for mediating variables. In contrast, the total indirect effect was statistically significant (indirect effect = 0.011, p < 0.001), indicating that the relationship between hypertension and depression is largely explained by intermediary pathways. Among individual mediators, subjective health status demonstrated the strongest indirect effect (β = 0.007, p < 0.001), followed by weight change (β = 0.001, p = 0.011). Current smoking showed a marginally significant indirect effect (p = 0.064). In contrast, aerobic physical activity, obesity, diabetes mellitus, and hypercholesterolemia were not significant mediators. Hypertension was significantly associated with several mediators, including high-risk drinking, smoking, subjective health status, weight change, obesity, diabetes, and hypercholesterolemia; however, only a subset of these pathways translated into meaningful indirect effects on depression. Overall model fit indices indicated acceptable fit (SRMR = 0.043; RMSEA = 0.073), supporting the robustness of the proposed mediation structure.

Conclusions

These findings suggest that the association between hypertension and depression is predominantly indirect and mediated through modifiable behavioral and subjective health pathways rather than a direct effect. In particular, perceived health status and weight-related changes appear to play central roles in linking hypertension to depressive symptoms. Interventions targeting health perception, lifestyle modification, and risk behaviors such as smoking may be critical for reducing depression risk among individuals with hypertension. Future longitudinal studies are warranted to confirm causal pathways and to explore the temporal dynamics of these associations in diverse populations.

References

1. Meng, L., Chen, D., Yang, Y., Zheng, Y., & Hui, R. (2012). Depression increases the risk of hypertension incidence: A meta-analysis of prospective cohort studies. Journal of Hypertension, 30(5), 842–851. https://doi.org/10.1097/HJH.0b013e32835080b7
2. Li, Z., Li, Y., Chen, L., Chen, P., & Hu, Y. (2015). Prevalence of depression in patients with hypertension: A systematic review and meta-analysis. Medicine, 94(31), e1317. https://doi.org/10.1097/MD.0000000000001317
3. Idler, E. L., & Benyamini, Y. (1997). Self-rated health and mortality: A review of twenty-seven community studies. Journal of Health and Social Behavior, 38(1), 21–37. https://doi.org/10.2307/2955359