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. 2020 Jun 1;77(6):598-606.
doi: 10.1001/jamapsychiatry.2019.4712.

Associations Between Depression, Arterial Stiffness, and Metabolic Syndrome Among Adults in the UK Biobank Population Study: A Mediation Analysis

Alex Dregan  1 , Lauren Rayner  1 , Katrina A S Davis  1 , Ioannis Bakolis  2   3 , Jorge Arias de la Torre  1 , Jayati Das-Munshi  1 , Stephani L Hatch  1 , Robert Stewart  1   4 , Matthew Hotopf  1   4
Affiliations

Associations Between Depression, Arterial Stiffness, and Metabolic Syndrome Among Adults in the UK Biobank Population Study: A Mediation Analysis

Alex Dregan et al. JAMA Psychiatry. .

Abstract

Importance: Previous research has linked a history of depression with arterial stiffness (AS) during midlife.

Objective: To assess the association of depression with elevated midlife AS and to investigate the extent to which this association is mediated via metabolic syndrome (MetS).

Design, settings, and participants: This population-based retrospective cohort study analyzed data collected between March 2006 and December 2010 from 124 445 participants aged 40 to 69 years from the UK Biobank. Participants without data on AS at baseline (n = 332 780) or who reported a previous diagnosis of cardiovascular disease (n = 45 374) were not eligible. Data analysis was performed from May to August 2019.

Exposures: Lifetime history of depression was assessed via verbal interview and linked hospital-based clinical depression diagnosis. Metabolic syndrome was defined as the presence of 3 or more of hypertension, dyslipidemia, hyperglycemia, hypertriglyceridemia, and unhealthy waist circumference.

Main outcomes and measures: Peripherally assessed AS index (ASI) using digital photoplethysmography.

Results: Of 124 445 included participants with ASI assessed, 71 799 (57.7%) were women, and the mean (SD) age was 56 (8) years. A total of 10 304 participants (8.3%) reported a history of depression. Study findings indicated a significant direct association between depression and ASI levels (β = 0.25; 95% CI, 0.17-0.32). A significant indirect association was also observed between depression and ASI levels (β = 0.10; 95% CI, 0.07-0.13), indicating that 29% of the association of depression with ASI was mediated by MetS. The proportion of mediation increased to 37% when C-reactive protein was added to the MetS criteria (direct association: β = 0.21; 95% CI, 0.15-0.28; indirect association: β = 0.13; 95% CI, 0.10-0.17). Concerning components of MetS, the strongest indirect association was for waist circumference, accounting for 25% of the association between depression and ASI levels (direct association: β = 0.26; 95% CI, 0.18-0.34; indirect association: β = 0.09; 95% CI, 0.06-0.11). Among men, hypertriglyceridemia accounted for 19% of the association between depression and ASI (direct association: β = 0.22; 95% CI, 0.05-0.40; indirect association: β = 0.05; 95% CI, 0.02-0.08).

Conclusions and relevance: One-third of the association of depression with elevated ASI levels during midlife may be accounted for by combined MetS and inflammatory processes. Unhealthy waist circumference and hypertriglyceridemia emerged as the most important potential targets for preventive interventions within women and men, respectively.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Das-Munshi has received grants from the Health Foundation and Academy of Medical Sciences. Dr Hatch has received grants from the Economic and Social Research Council, Guy’s and St Thomas’ Charity, National Institute for Health Research, and the Wellcome Trust and is a member of the Mental Health Delivery Group: Workforce Equalities Subgroup, Health Education England, and the Workforce Race and Equality Standard of the NHS England Strategic Advisory Group. Dr Stewart has received grants from Janssen Pharmaceuticals and has cosupervised PhD students for GlaxoSmithKline and Takeda Pharmaceuticals. Dr Hotopf has received grants from King’s College London, Innovative Medicines Initiative, and European Federation of Pharmaceutical Industries and Associations. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Mediating Pathway of the Association of Depression With Arterial Stiffness
Direct acyclic graph of a structural model of mediation of the association between depression and arterial stiffness by metabolic syndrome. NDE indicates natural direct effects; NIE, natural indirect effects.
Figure 2.
Figure 2.. Mean Arterial Stiffness Index
Sex-specific mean arterial stiffness index values. Boxes contain 50% of the data, and the error bars contain the remainder. The horizontal lines indicate medians.
See this image and copyright information in PMC

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