Qin Pei, Gong Jessica, Steptoe Andrew, Fancourt Daisy
Department of Behavioural Science and Health, Institute of Epidemiology & Health Care, University College London, London, UK.
Department of Epidemiology & Public Health, Institute of Epidemiology & Health Care, University College London, London, UK.
medRxiv. 2025 Aug 11:2025.08.07.25333199. doi: 10.1101/2025.08.07.25333199.
Social support has been related to cardiovascular disease (CVD) incidence and mortality in longitudinal cohort analyses, but the biological pathways underpinning this remain underexplored. We explored the protein signatures of social support amongst older adults and the mediating effect of proteins in the association between social support and CVD and mortality.
Data from 3,141 adults over the age of 50 in the English Longitudinal Study of Ageing who had plasma proteome data were analysed, with CVD and mortality outcomes followed up for 16 years following through Hospital Episode Statistics and the National Health Service 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 examine 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 proteins measured, greater social support was associated with lower levels of 13 proteins (EFNA4, SKR3, TNFRSF10A, TNFRSF11A, TRAIL-R2, Gal-9, FGF-23, REN, VSIG2, AMBP, MMP12, ASGR1, PSG1) and higher TN-R levels, after adjusting for baseline socioeconomic confounders. Of these 13 proteins, six proteins (TNFRSF10A, TNFRSF11A, FGF-23, VSIG2, AMBP, and ASGR1) were significantly associated after full adjustments. We also identified 49 protein-CVD and 70 protein-mortality associations after minimal adjustments, including 11 and 14 proteins simultaneously associated with social support. In the mediation analysis, each protein showed significant indirect effects: 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 proteomic signatures and these proteins 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, proteins, and CVD and mortality development.
在纵向队列分析中，社会支持与心血管疾病（CVD）的发病率和死亡率相关，但其背后的生物学途径仍未得到充分探索。我们探讨了老年人社会支持的蛋白质特征，以及蛋白质在社会支持与CVD及死亡率之间关联中的中介作用。
对英国老龄化纵向研究中3141名年龄在50岁以上且有血浆蛋白质组数据的成年人的数据进行分析，通过医院事件统计和国民健康服务中央登记处对CVD和死亡率结局进行了16年的随访。采用线性回归和Cox回归分析来确定与社会支持、CVD和死亡率相关的蛋白质。然后对确定的蛋白质进行中介分析，以检验它们作为社会支持与CVD及死亡风险之间潜在中介的作用。
在中位15.8年的随访期内，889名参与者死亡，627人患CVD。在测量的276种蛋白质中，在调整基线社会经济混杂因素后，更高的社会支持与13种蛋白质（EFNA4、SKR3、TNFRSF10A、TNFRSF11A、TRAIL-R2、Gal-9、FGF-23、REN、VSIG2、AMBP、MMP12、ASGR1、PSG1）水平降低以及TN-R水平升高相关。在这13种蛋白质中，经过全面调整后，6种蛋白质（TNFRSF10A、TNFRSF11A、FGF-23、VSIG2、AMBP和ASGR1）具有显著相关性。在进行最小调整后，我们还确定了49种蛋白质与CVD以及70种蛋白质与死亡率之间的关联，其中包括11种和14种同时与社会支持相关的蛋白质。在中介分析中，每种蛋白质均显示出显著的间接效应：所有显著蛋白质共同分别介导了CVD和死亡率关联的约20.9%和26.4%。主要富集的生物学途径涉及死亡受体活性和碳水化合物结合。
社会支持与蛋白质组特征相关，这些蛋白质独立且累积地介导了社会支持与CVD及死亡风险之间的关联。这些发现加深了我们对人际关系质量、蛋白质以及CVD和死亡率发展之间复杂联系的理解。
