Work

Multidimensional sleep health: risk of cardiovascular disease and mortality, and mediation by plasma proteins

Year: 2026

Type: article

Abstract: Background: Sleep health is a recognised determinant of cardiovascular health, but most previous research has examined individual sleep traits in relation to cardiovascular disease and mortality. The molecular pathways linking multidimensional sleep health to these outcomes remain insufficiently explored. We aimed to examine these associations and identify circulating proteins showing potential mediation signals in these relationships. Methods: We analysed data on 257,509 individuals from the UK Biobank, including 26,984 with available plasma proteomic data. Using baseline questionnaire data collected by UK Biobank, we calculated a seven-component sleep health score (SHS) and derived data-driven sleep patterns using K-prototypes clustering. We used multivariable Cox proportional hazards models to examine the associations of the SHS and, separately, the sleep patterns with incident coronary heart disease, stroke, atrial fibrillation and heart failure, as well as cardiovascular and overall mortality. Lastly, we identified SHS-related proteins using linear regression, with representative proteins selected using least absolute shrinkage and selection operator regression, and mediation analyses performed. Results: Higher SHS was associated with lower risks of coronary heart disease, stroke, atrial fibrillation, heart failure, cardiovascular mortality, and overall mortality, with the strongest associations observed for heart failure and coronary heart disease. Mixed sleep disturbance and non-restorative sleep patterns were associated with higher risks across multiple outcomes. Proteomic analyses identified 188 SHS-related proteins, mainly enriched in inflammatory, immune, and chemotactic pathways. Exploratory mediation analyses identified 34 proteins with potential mediation signals, among which HGF, IGF2R, and FABP4 showed recurrent cross-outcome signals. Conclusions: Poor multidimensional sleep health was associated with higher cardiovascular disease and mortality risks, with exploratory proteomic analyses suggesting potential involvement of circulating proteins related to inflammation, immunity, chemotaxis, and metabolic dysregulation. These findings support multidimensional sleep assessment as a population-level prevention strategy and provide candidate molecular pathways for future mechanistic and interventional studies.

Source: Journal of Global Health

DOI: 10.7189/jogh.16.04349