Plasma proteomic signatures of social support and their association with cardiovascular disease and mortality: exploratory analyses in a national cohort study

Social support has been related to cardiovascular disease (CVD) incidence and mortality in longitudinal cohort analyses, but the biological pathways underpinning this remain underexplored. This exploratory study examined the associations between social support and a wide range of proteomic biomarkers and performed the mediating effect of proteomic biomarkers in the association between social support and CVD and mortality to identify potential biological pathways linking social support to health outcomes. Data from 3141 adults over the age of 50 in the English Longitudinal Study of Ageing who had plasma proteome data were analyzed, with CVD and mortality outcomes followed up for 16 years following through Hospital Episode Statistics and the National Health Service’s Central Registry. Linear and Cox regression analyses were used to identify proteins associated with social support, CVD, and mortality. Mediation analysis was then performed on the identified proteins to explore their role as a potential mediator between social support and CVD and mortality risk. Over a median of 15.8-year follow-up, 889 participants have died, and 627 developed CVD. Of 276 plasma proteins measured, greater social support was associated with lower levels of 13 proteins and higher TN-R levels, after adjusting for baseline socioeconomic confounders. We also identified 49 protein-CVD and 70 protein-mortality associations after minimal adjustments, including 11 and 14 proteins simultaneously associated with social support. All the significant proteins together mediated about 20.9% and 26.4% of the associations for CVD and mortality, respectively. The main enriched biological pathways involved death receptor activity and carbohydrate binding. Social support was related to a cluster of proteomic biomarkers, which may be linked to inflammation, apoptosis, and atherosclerosis/vascular pathways. The identified plasma proteins partly mediated the association between social support and CVD and mortality risk, independently and cumulatively. These findings deepen our understanding of the intricate connections between relationship quality, proteomic signatures, and CVD and mortality development.