Mental health conditions and cardiovascular diseases: associations and risk stratification based on genetics, lifestyle, and biomarkers

Nakada, Shinya (2026) Mental health conditions and cardiovascular diseases: associations and risk stratification based on genetics, lifestyle, and biomarkers. PhD thesis, University of Glasgow.

Abstract

Multimorbidity involving a common mental health condition (MHC) such as anxiety or depression and a concomitant cardiovascular disease (CVD) poses a high public health burden globally. However, health services and research are largely structured around single systems, rather than adopting a holistic approach. Given the emerging evidence that MHCs could increase the risk of CVD, understanding the roles of MHCs in developing CVD could inform preventive strategies and, thereby, may help to reduce burden.

UK Biobank is a very large-scale population cohort study, designed to investigate extensive environmental, lifestyle, and genetic risk factors related to a wide range of health conditions in adults. Utilising the UK Biobank, it is possible to undertake a systematic investigation of MHC-CVD clustering using various types of data and epidemiological approaches.

My thesis aimed to investigate the roles of anxiety and depression in developing CVD in middle-aged and older adults using data from UK Biobank. Specific objectives were to: (1) examine the individual and joint associations of anxiety and depression with a range of incident CVD outcomes; (2) examine the associations of anxiety and depression with CVD stratified by CVD genetic susceptibility; (3) examine the extent to which lifestyle, physical, and metabolic factors mediate the associations between anxiety and depression and incident CVD; and (4) examine whether including anxiety and depression in an existing CVD risk score improves the prediction of CVD risk.

To achieve the aim, my thesis included four published manuscripts, each addressing one objective. Collectively, my findings contributed to the elucidation of the roles of anxiety and depression in developing CVD and identified actionable pathways. Therefore, the findings generated not only advance current understanding but also have direct clinical and public health relevance.

Firstly, I found that having anxiety contributed the same relative excess risk of CVD regardless of the presence of depression, and vice versa, suggesting that anxiety and depression operate independently and therefore both warrant attention in CVD risk management. Secondly, CVD genetic susceptibility partly contributed to the clustering of depression and CVD but did not provide a full explanation, nor did it explain the association between anxiety and CVD. Therefore, the increased risk of CVD in these patients should be addressed regardless of CVD genetic susceptibility. Thirdly, smoking and central obesity were the strongest lifestyle and physical mediators of CVD for both anxiety and depression. However, high systolic blood pressure was the strongest metabolic mediator for anxiety whilst C-reactive protein was the strongest metabolic mediator for depression. The findings inform a more personalised risk management among people with anxiety or depression. Lastly, I found that incorporating measures of anxiety and depression into an existing CVD risk score significantly, but only modestly, improved prediction of CVD onset. Whether to integrate MHCs into CVD risk scores should be carefully considered, especially when it attracts additional costs, and investigating broader MHCs using established tools or diagnostic interview data could be the focus of future studies.

Overall, these findings highlight the need to assess and manage CVD risk factors among people living with anxiety and depression in order to reduce their burden from CVD.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Supported by funding from the Medical Research Council (MR/N013166/1-LGH/MS/MED2525).
• Subjects: B Philosophy. Psychology. Religion > BF Psychology; Q Science > QH Natural history > QH426 Genetics; R Medicine > R Medicine (General)
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Mental Health and Wellbeing
• Funder's Name: Medical Research Council (MRC)
• Supervisor's Name: Ho, Professor Frederick and Pell, Professor Jill
• Date of Award: 2026
• Depositing User: Theses Team
• Unique ID: glathesis:2026-86307
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 06 Nov 2026 15:05
• Last Modified: 06 Nov 2026 15:09
• Thesis DOI: 10.5525/gla.thesis.86307
• URI: https://theses.gla.ac.uk/id/eprint/86307

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