Relationship Between Arterial Stiffness and Depression Mediated by Metabolic Syndrome, Inflammation

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Metabolic syndrome, including hypertension, obesity, dyslipidemia, and hyperglycemia, promote arterial stiffness, which has been linked to depression.

Metabolic syndrome and inflammation account for one-third of the association between depression and arterial stiffness (AS), according to findings published in JAMA Psychiatry as part of a population-based retrospective cohort study.

Patients with depression are at increased risk of AS and subsequent major cardiovascular events (MACEs), including coronary heart disease and stroke. Metabolic syndrome, including hypertension, obesity, dyslipidemia, and hyperglycemia, promote AS, but the extent to which the link between AS, MACE, and depression is mediated by metabolic syndrome is unknown.

Alex Dregan, PhD, of the department of psychological medicine, Institute of Psychiatry, Psychology, and Neuroscience, King’s College London, United Kingdom, and colleagues assessed peripheral AS index (ASI) using digital photoplethysmography in 124,445 patients (mean age, 56±8 years; 57.7% women) from the UK Biobank. A history of depression, determined through interviews and clinical diagnosis, was reported by 10,304 patients (8.3%).

The researchers found significant direct (β = 0.25; 95% CI, 0.17-0.32) and indirect (β = 0.10; 95% CI, 0.07-0.13) associations between depression and ASI levels, with the latter relationship indicating that metabolic syndrome mediates 29% of the association of depression with ASI. This percentage rose to 37% when C-reactive protein was included in the metabolic syndrome criteria (direct association: β = 0.21; indirect association: β = 0.13). Waist circumference demonstrated the strongest indirect association (25%) between depression and ASI levels (direct association: β = 0.26; indirect association: β = 0.09). Hypertriglyceridemia accounted for 19% of the association between depression and ASI (direct association: β = 0.22; indirect association: β = 0.05) in men.

The study contributes to ongoing research efforts to understand the risk for MACE associated with depression, and specifically to the contributions played by metabolic syndrome and inflammatory processes. “To our knowledge, this is the first study to document that the association between depression and increased AS may be partly mediated via [metabolic syndrome],” the investigators contended.

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Study limitations include the possibility of no exposure-induced mediator-outcome confounding and the self-reported data on depression.

The researchers concluded, “Our study findings identified that about one-third of the proportion of the association between depression and ASI, and consequently, the risk of MACE, may be potentially prevented by addressing the combined effects of [metabolic syndrome] and inflammation.”

Disclosure: The study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of disclosures.


Dregan A, Rayner L, Davis KAS, et al. Associations between depression, arterial stiffness, and metabolic syndrome among adults in the UK Biobank Population Study. A mediation analysis [published online January 29, 2020]. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2019.4712